The present invention relates to a process for the preparation of alpha-pivaloyl-substituted acetic acid esters.
The alpha-pivaloyl-substituted acetic acid esters which may be prepared by practice of the process of the invention are known compounds having utility as photographic chemicals and as pharmaceutical intermediates. Particular examples of these compounds are methyl pivaloylacetate disclosed in French Pat. No. 2,191,887, in British Pat. Nos. 1,483,948 and 1,491,606, and in a publication by F. W. Swamer and C. R. Hauser (J. Amer. Chem. Soc., 72 (1950), 1352), and ethyl pivaloylacetate disclosed in U.S. Pat. No. 3,142,692.
Several routes are known in the art for production of sterically hindered aliphatic beta-keto esters, such as the alpha-pivaloyl acetic acid esters. Generally, the yields of desired product are low under known synthesis procedures, a result of the formation of a variety of side products. Steps which can be taken to improve the yields of conventional processes are commercially impractical, because they require the use of expense reagents and/or solvents.
The present invention particularly relates to a preparation of alpha-pivaloyl-substituted acetic acid esters in which pivaloyl malonic acid esters are subjected to reaction with specific bases and the reaction product subsequently acidified. It is considered surprising that this route can be readily followed to prepare the alpha-pivaloyl-substituted acetic acid esters, since acyl malonic acid esters are known to undergo rapid deacylation in base-catalyzed reactions to give acids in high yield (Cahiers de Synthese Organique, Vol. V (1959), p.254) and also to degrade to corresponding ketones when treated with acid (Ibid, p.63). By means of the process of the invention, however, it is found to be possible to cleave the pivaloyl malonic ester, replacing one of its two ester moieties with hydrogen, while maintaining the pivaloyl moiety and one ester moiety in the same molecule.